Novel phytopeptide osmotin mimics preventive effects of adiponectin on vascular inflammation and atherosclerosis
Abstract
Introduction The novel phytohormone, osmotin, has been reported to act like mammalian adiponectin through PHO36/AdipoR1 in various in vitro and in vivo models. However, there have been no reports regarding the precise effects of osmotin on atherosclerosis.Methods We assessed the atheroprotective effects of osmotin on inflammatory molecules in human umbilical vein endothelial cells (HUVECs), human leukemic monocyte (THP-1) adhesion, inflammatory responses, and foam cell formation in THP-1-derived macrophages, and the migration, proliferation, and extracellular matrix expression in human aortic smooth muscle cells (HASMCs). We examined whether 4-week infusion of osmotin could suppress the development of aortic atherosclerotic lesions in apolipoprotein E-deficient (ApoE-/-) mice.Results AdipoR1 was abundantly expressed in HUVECs, HASMCs, THP-1, and derived macrophages. Osmotin suppressed lipopolysaccharide-induced upregulation of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein-1, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin in HUVECs, and TNF-α-induced THP-1-HUVEC adhesion. In THP-1-derived macrophages, osmotin suppressed the inflammatory M1 phenotype, lipopolysaccharide-induced secretion of interleukin-6 and TNF-α, and oxidized low-density lipoprotein-induced foam cell formation associated with CD36 and acyl-CoA:cholesterol acyltransferase 1 downregulation and ATP-binding cassette transporter A1 upregulation. In HASMCs, osmotin suppressed angiotensin II-induced migration, proliferation, collagen-1 and fibronectin expression, and matrix metalloproteinase-2 activity without inducing apoptosis. Infusion of osmotin into ApoE-/- mice prevented the development of aortic atherosclerotic lesions with reductions of intraplaque pentraxin-3 expression, fasting plasma glucose, and insulin resistance.Conclusions This study provided the first evidence that osmotin exerts preventive effects on vascular inflammation and atherosclerosis, which may facilitate the development of new therapeutic modalities for combating atherosclerosis and related diseases.
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Osmotin has potential effects for counteracting obesity, diabetes and cardiovascular diseases.
“Several in vitro and in vivo studies revealed its potential effects for counteracting obesity, diabetes and cardiovascular diseases [125,126,127].”
From Adiponectin and Its Mimics on Skeletal Muscle: Insulin Sensitizers, Fat Burners, Exercise Mimickers, Muscling Pills … or Everything Together? (2020) · cites this paper as [127]
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Gasbarrino, K., Boutari, C., Filippaios, A., Gianopoulos, I., Daskalopoulou, S. S., & Mantzoros, C. S. (2023) · Contemporary cardiology · doi:10.1007/978-3-031-13177-6_8 · Cited by 1 · see citing works
Geng, D., Ju, Z., Xiao, T., Zhou, S., Huang, L., Liu, L., Zhou, X., Wang, L., & Tong, L. (2020) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-020-10097-5
“Numerous studies have shown that bioactive peptides, such as IRW derived from egg protein and osmotin derived from Nicotiana tabacum, can protect vascular cells by reducing inflammatory response (Huang et al. 2010; Takahashi et al. 2018).”
BackgroundPineda, A. L. M., Maria, C., Fernando, L.-S., Alma, C., Manuel, G.-M., Martin, A.-B., Juan, M., & Soto-Guzmán, A. (2023) · Medical Research Archives · doi:10.18103/mra.v11i8.4198
Costa, V., Aluan, K., Schiavetti, I., Bason, C., Vigo, T., Leveraro, E., Cabona, C., Prada, V., Costagli, M., Boccia, V. D., et al. (2025) · PLoS ONE · doi:10.1371/journal.pone.0311214
Zhu, J. F., Guo, J., Liu, J., Chen, C., Chen, H., Wang, C., Yuan, A., Lu, D., & Le, Y. (2026) · Phytotherapy Research · doi:10.1002/ptr.70419
“…and adhesion factor expression in endothelial cells, inhibits macrophage pro-inflammatory phenotypes and foaming, attenuates angiotensin II-induced smooth muscle cell migration, proliferation, and pro-fibrotic phenotypes, and prevents aortic atherosclerotic lesions (Takahashi et al. 2018).”
- Authors
- Takahashi, Y., Watanabe, R., Sato, Y., Ozawa, N., Kojima, M., Watanabe-Kominato, K., Shirai, R., Sato, K., Hirano, T., & Watanabe, T.
- Affiliations
- Tokyo University of Pharmacy and Life Sciences (JP)
- SHOWA Medical University (JP)
- Corresponding author
- Watanabe, Takuya
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 83
- Pages
- 128-138
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2790671057
- Cited by
- 40
- References
- 51
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 4
- FWCI
- 4.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- osmotin, adiponectin, AdipoR1, vascular inflammation, atherosclerosis, endothelial inflammation, macrophage foam cell formation, smooth muscle cell proliferation and migration, extracellular matrix, insulin resistance, ApoE-deficient mice, pentraxin 3, anti-inflammatory activity
- MeSH terms
- Anti-Inflammatory Agents, Cells, Cultured, Foam Cells, Humans, Inflammation, Macrophages, Muscle, Smooth, Vascular, Plant Proteins, Cytoprotection, Myocytes, Smooth Muscle, Biomimetics, Atherosclerosis, Adiponectin, Human Umbilical Vein Endothelial Cells
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